Genetically altered tobacco fights cervical cancer
Nozipho Mthembu
Scientists at UCT are using genetically altered tobacco plants to create
vaccines against cervical cancer. They aim to create vaccines that fight the
virus not the wallet. Read how.
Rows of bright green, leafy tobacco plants grow in a humid greenhouse. They
look identical but one row is special. These are genetically altered tobacco
plants, carrying the shell of the human papilloma virus which causes cervical
cancer in women.
Tobacco leaves, dried, rolled and smoked, cause lung cancer. But these
genetically modified tobacco leaves are little factories, producing a
potentially inexpensive vaccine against cervical cancer, the biggest cancer
killer of women in Southern Africa and one which is particularly difficult to
catch early as it is buried deep within the female reproductive system.
The tobacco plant is an ideal crop for genetic modification. For a start, the
genetic alteration doesn’t confer any survival advantage over plants that have
not been tweaked. In addition, tobacco and humans have been around each other
for so long that they have developed a reliance on each other: the plant can’t
escape and grow wild. Just like maize, tobacco requires human intervention to
survive in Africa.
"Tobacco is a really well understood crop," says Professor Ed
Rybicki of the University of Cape Town. "All of the kinds of conditions
that one needs to use to grow it are very well understood indeed. It is
relatively tolerant of all sorts of conditions and you get an enormous volume of
leaf out of each plant, one hectare of mature tobacco gives you 20,000 kilograms
or 20 metric tons of wet leaf. So that is an enormous volume of plant material
that you can actually make something out of."
Tobacco
What Rybicki and his team are trying to make out of tobacco is an affordable
vaccine against the virus which causes cancer in the cervix, the gateway between
the vagina and the uterus. (Men can transmit the virus. They can also develop
cancer of the penis. However, men have a far lower rate of penile cancer,
compared to cervical cancer in women, so it’s not quite the same public health
issue.)
"You start with trying to make something that the immune system is going
to recognise instead of the virus. You cannot use the live virus because you
cannot culture these particular viruses, it is almost impossible," says the
Zambia-born viral biotechnologist. "So what you do is make a portion of the
virus - that is, the protein coat - which is what the immune system recognises.
You can make this in a number of systems. And the nice thing about it is however
you make it, it usually self-assembles - that is, it makes something that looks
like the real virus. We can make it in animal cell cultures, we can make it in
insect cell cultures, we can make it in plants. And we are trying to make plant
production a reality."
The hollowed-out virus lacks nucleic acid, the trigger which makes the virus
infectious. Consider a jacket or coat without anyone inhabiting it. It lies limp
and flat. The same thing applies to this protein coat. Give a human the
hollowed-out virus, with the outside intact, and the body’s immune system goes
on attack. If the real virus shows up, transmitted by sex, it doesn’t stand a
chance.
Plant vaccine factories
"The primary reason for making things like vaccines in plants is that it
is potentially cheap," Rybicki said. "We may be able to cut costs by
orders of magnitude, because you do not need a fermentation plant which you
would for yeast or bacteria, you don't need huge tissue culture facilities which
you would need for human or insect or animal tissue culture. What you need is a
field or probably more likely a greenhouse."
The particles are also relatively easy to purify. They are "nice big
stable particles, which cannot do anything except provoke a response."
Like any vaccine developers, the team is far from their goal – and
relatively comfortable with that.
Vaccines that attack the virus not the wallet
"The usual vaccine production pathway from initiation of research to
production is about 10 years and there is a lot of reiteration because you have
to discover how to do things better or even how to do things at all," said
Rybicki. "We are still in the development phase. We have got candidates, we
know that we can make them. We need to make them on a bigger scale, prove that
we can make them economically and then stick them in a bottle. Only then will we
begin animal testing, let alone human testing."
South Africa used to have the capacity to generate its own polio virus
vaccine in the 1950s. Now it imports. In his office at the Department of
Molecular and Cell Biology, Rybicki notes that simply working on a vaccine
carries significant advantages for developing countries: "there are a lot
of orphan diseases out there that nobody wants to make a vaccine for. Vaccines
cost about one hundred million US dollars to take through from beginning to
human testing, just through to human testing, and this is enormous money for big
pharmaceutical companies. Drug development can cost even more than vaccine
development but because the vaccine market is so much smaller than the drug
market, the return is relatively low."
The number of vaccines being made today has dropped to its lowest in a
quarter of a century. Some vaccines have become a victim of their own success: a
one-off dose of polio drops generates considerably less money than say,
anti-depressant pills which have to be taken every day for the rest of the
patient’s life.
But there are major international efforts underway in countries such as
India, Brazil, China and Argentina to make publicly funded vaccines.
"Diseases that don't occur in Europe or the United States do not get
vaccines made for them. Or they don’t get the right type of vaccine. In
Africa, we won’t necessarily get the correct HIV subtype vaccine made for
example."
Also, new vaccines made in Europe or the US are expensive. "The
Hepatitis B vaccine when it first came out was around 40$ a dose and it is now
about a dollar a dose but it took ten or 15 years to get to that point!"
marvelled Rybicki. The current push by big pharmaceutical companies for a
vaccine for cervical cancer – already well advanced, with the first human
trials accomplished - doesn’t worry him. The vaccine will be too expensive for
third world health budgets, he predicts. His aim is to find something that
attacks the virus, not the wallet.
More information:
Dr Ed Rybicki: ed@science.uct.ac.za
www.mcb.uct.ac.za/staff/ed/htm
Public understanding of Biotechnology website www.pub.ac.za
|
